The current proposal requests funds for the purchase of an ABI SOLiD V3 sequencer, a next- generation, and massively parallel sequencing platform. The ultra-high throughput of next- generation instruments, coupled with substantially reduced sequencing costs have made these the platforms of choice for interrogating genome sequence and function. Massively parallel sequencing is particularly well-suited for epigenomic and functional genomics studies, including chromatin structure, histone modifications and variants, regulatory factor localization;DNA methylation;transcription;and quantification of genome modifications such as localization of retroviral vector integrations. With 2-base encoding, the SOLiD V3 system is capable of generating highly accurate sequence data, with an output of >20 gigabases of mappable data per run, from >400 million mappable reads from the two slides with each run of the instrument. This output is roughly double that of other short read sequencers currently on the market, and, with read lengths expected to reach 100 bases by early 2010, the raw sequence output will double again. Demand for next-generation sequencing capacity is experiencing explosive growth as more investigators realize the potential of the technology to impact and accelerate their research. The new instrument will be deployed in the context of a well-established, self- supporting core facility that already provides substantial epigenomics-focused next-generation sequencing services and associated bioinformatics support, and is therefore ideally positioned to rapidly translate the SOLiD V3's potential to meet the needs of specific investigator projects as well as those of the general research community. PUBLIC HEALTH RELEVANCE: The current proposal requests funding to purchase an ABI SOLiD v3 massively parallel sequencing platform. The new instrument will be deployed in the context of an existing core facility, and will address substantial demand for epigenomic and functional genomics sequencing applications including mapping and analysis of chromatin structure, regulatory factors, and DNA methylation. The instrument will also support gene therapy programs by providing a platform to map genomic sites of therapeutic vector integration in model and patient cells.